Familial breast cancer not only inherited genetically

Researchers at The University of Melbourne have identified heritable but non-genetic markers for breast cancer susceptibility, in a breakthrough that will enable doctors to better predict breast cancer risk.

Mutations in known breast cancer genes such as BRCA1 and BRCA2 are identified in only approximately 20% of women who are offered genetic testing for familial breast cancer. The other 80% receive no explanation for their breast cancer predisposition, according to Professor Melissa Southey.

Seeking to rectify this, Professor Southey and her team looked at 210 people from 25 multiple-case breast cancer families. They identified 24 previously unknown epigenetic changes that alter a woman’s risk of breast cancer and can be passed down through generations without involving changes in the DNA sequence of genes.

Published in the journal Nature Communications, the study looked at epigenetic changes called DNA methylation, where methyl group chemicals modify DNA without changing its sequence. DNA methylation can mimic genetic variation, predisposing a family to breast cancer.

“Our methods were very successful when applied to breast cancer, and the exciting thing is that they can be applied to many other hereditary diseases,” said University of Melbourne statistician Dr James Dowty. “This work was the result of a very fruitful collaboration between molecular biologists and statisticians, like a lot of work in modern medical research.”

“Some individuals know they come from a family with a lot of breast cancer but do not have a mutation in a known breast cancer gene,” added research fellow Dr Eric Joo. “This study should help answer why some of those families have a lot of cancer. It’s very exciting to be unlocking part of a big puzzle.”

The study is one of the first to systematically scan the genome for places where DNA methylation is heritable, and is said to be the first to apply this to familial breast cancer. Dr Joo hopes more work will be done to develop tests to screen for the methylation markers associated with breast cancer.

“This groundbreaking work is not only helpful for women from families with many cases of breast cancer, it will improve breast cancer risk prediction for all women, and pave the way for the development of epigenetic therapeutics for breast cancer,” said Professor Southey.

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